Author summary: Living modified organisms containing engineered gene drives (EGD-LMOs) are designed to spread genetic modifications through wild populations and persist – a novel technology that brings with it fresh biosafety challenges. In light of these concerns, a set of guidance materials to support risk assessment of EGD-LMOs has been drawn up by a group of experts and welcomed by Parties to the Cartagena Protocol on Biosafety. However, the guidance materials advocate a narrow approach under which only what are identified as “plausible pathways to harm” are selected for assessment. This methodology fails to sufficiently address the central risks of gene drives arising from their very design objective – spread and persistence. Instead of being limited in scope, risk assessment should cast the net widely to capture all potential harms of EGD-LMOs. Only then will it align with the precautionary principle that is enshrined in the Cartagena Protocol and that will ensure adequate protection from the possible adverse effects of this controversial technology on biodiversity and human health.